PROJECT SUMMARY/ABSTRACT This is a renewal application for a high successful program designed to attract and train both predoctoral and postdoctoral investigators in basic investigation of childhood diseases related to cardiovascular and pulmonary biology. The need for a training program in the cellular and molecular basis of cardiovascular and pulmonary disease, especially of physician scientists interested in childhood diseases, is based upon clear evidence of a declining national pool of such individuals at both the faculty and trainee levels. Currently, few pediatric cardiology or pulmonary fellowship programs in American medical centers provide adequate training in this area of research, either at the bench or in structured clinical investigation. Our program is designed to address this need from two important perspectives: 1) To allow pediatric and other clinical fellows with an interest in basic research to develop research competence and career training; 2) To attract and train talented basic scientists at the pre- and post-doctoral levels to study mechanisms related to cardiorespiratory disease in childhood. Our program has been shaped by feedback from reviewers of the previous program, by advice from our faculty and program advisors, by past trainees, and by the inclusion of new faculty and core programs at Washington University that allow us to expand the training experience of our trainees. In addition to continuing our strong training in developmental/cell biology and the molecular basis of disease, the proposed program will take advantage of institutional strengths in genetics, stem cell biology, genomics, and bioinformatics?all of which are components of the foundation of modern research. In addition, we have a newly incorporated focus on infection of the cardiorespiratory system, a leading cause of pediatric morbidity and mortality worldwide. We have maintained a training curriculum for 4 postdoctoral and 2 predoctoral fellows with an uninterrupted 2-3 year block of full-time investigation. This focus is enhanced by a multidisciplinary core of didactic seminars, journal clubs and formal coursework that are designed for each trainee through consultation with the mentor/program administrators to provide individualized education in key aspects of cardiopulmonary development and disease. Our objectives are: 1) to provide extensive mentoring to the trainee for career development and for developing independent research plans that focus on pediatric diseases; 2) to promote training in basic cell and molecular biology, genomics, and bioinformatics together with clinical translational research; and 3) to guide our trainees? development so that, after the completion of training, successful competition for independent funding is likely.